Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Macrophages may play a significant role in the initiating stages leading to chronic inflammation/infection in cystic fibrosis (CF), via an inability to act as a suppressor cell. In a previous study demonstrating impaired function of CF macrophage, we have shown high production of soluble CD14 (sCD14). The aim of the present work is to determine origin and function of sCD14 in blood monocyte-derived macrophages from stable adult CF patients. Methods To study origin, sCD14 is measured by ELISA in supernatant of macrophages from healthy subjects (non-CF) treated with PI-PLC or cholesterol. The involvement of sCD14 in inflammation, was investigated by analysis of NF-kB and caspase 1 pathways in non-CF macrophages treated by sCD14. Measurement of gene expression was done by qPCR and proteins were quantified by ELISA and Western blot. Results Treatment with PI-PLC increased sCD14 level in the supernatant of non-CF macrophages whereas cholesterol did not modified it. Furthermore high secretion of sCD14 from CF macrophages was decreased by an inhibitor of PI-PLC. Treatment with sCD14 increased pro-IL-1β, IL-8 and TNF-α expression resulting from NF-kB activation through IkBa phosphorylation, this effect was inhibited by NF-kB inhibitors. Also, activation of caspase 1 by cleavage of pro-caspase 1 allowed the secretion of mature IL-1β, inhibited by an inhibitor of caspase 1. However, inflammasome complex involved in caspase 1 activation remains to be determined. Conclusion This data show that origin of sCD14 is partly due to the action of lipases cutting the GPI tail that serves as a membrane anchor to CD14. Furthermore sCD14 have a role in chronic inflammation in CF
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162773
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162773
DOI : 10.1016/S1569-1993(15)30203-4

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
INTRODUCTION:The AIRBAg study screens for bronchial obstruction in dairy farmers. We present the preliminary results after one year.METHODS:A prospective screening study based on questionnaires and electronic mini-spirometry (Néo-6(®)) that includes a representative sample of dairy farmers from the departments of Morbihan and Île-et-Vilaine in Brittany. The dairy farmers had an occupational medicine appointment and, if they demonstrated at least one marker of possible bronchial obstruction (chronic cough, chronic bronchitis, dyspnoea, wheezing, FEV1/FEV6<0.8), they were referred to a pulmonologist. The data we present here were extracted from the occupational medicine appointments because the pulmonologists' appointments are still running.RESULTS:Among the 277 dairy farmers included, 125 (45%) demonstrated "possible bronchial obstruction". The total score of the CAT questionnaire was higher in these farmers (9.1±6.2 versus 5.8±4.0; P<0.0001). In multivariate analysis markers of "possible bronchial obstruction" were eczema, manual foddering and duration of mechanical straw litter spreading.CONCLUSION:Occupational medicine appointments identified markers of "possible bronchial obstruction". We will have the complete results from AIRBAg study in 2015.
ISSN: 0761-8425

hal-01117944
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117944
DOI : 10.1016/j.rmr.2014.03.014
PUBMED : 25847201

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Oxidative stress, excess production of reactive oxygen species (ROS) and intense colonization of the respiratory tract by microorganisms are described in CF patients, leading to an influx in macrophages. This results in activation of NADPH oxidase that yields ROS, initiating the oxidative burst responsible for pathogen destruction. We showed that phagocytosis was altered in CF macrophages, yet oxidative status in this cell was not defined. The objective of this study is to draw a link between oxidative stress and plasma membrane integrity in CF macrophages, since lipid peroxidation is known to alter cell membrane. Methods Peripheral blood monocytes-derived macrophages were obtained from CF patients and healthy subjects. Plasma membrane fluidity was assessed with di4-ANEPPDHQ and oxidative status was measured with ROS indicating probes. Results In CF macrophages, membrane fluidity was increased whereas lipid peroxidation was diminished. Surprisingly, general oxidative status remained similar to the one observed in non-CF macrophages. Also, CF macrophages did not abolish chemically induced-oxidative stress. In non-CF macrophages, treatment with cholesterol slightly increased membrane fluidity whereas LPS treatment had no effect. Conclusion CF macrophages displayed an increased membrane fluidity associated with a decreased lipid peroxidation. This raises the hypothesis that membrane alteration in CF macrophages may be due to other mechanism than oxidative stress. Nevertheless, since the killing capacity of CF macrophage is defective, a deregulation of O•−2 production is very likely, suggesting alteration of NADPH oxidase or mitochondrial dysfunction
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162769
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162769
DOI : 10.1016/S1569-1993(15)30217-4

Éditeur(s) : HAL CCSD
Résumé : International audience
Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.
Revue Des Maladies Respiratoires

hal-01560287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560287
DOI : 10.1016/j.rmr.2017.03.034
PUBMED : 28552256

Éditeur(s) : HAL CCSD
Résumé : International audience
Journal of Cystic Fibrosis
Dublin, Ireland

hal-01122611
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122611
DOI : 10.1016/S1569-1993(12)60121-0